The understanding of the anti-viral and anti-tumor immune responses requires the studies of the molecular mechanisms of the lysis of virus- infected or tumor cells by effector lymphocyte subpopulations. Thus, our efforts are directed toward the: A) implication of specific CD8+ and/or CD4+ cells in the anti-tumor response and B) identification of key enzymes in CTL and in target cells that participate in the "lethal hit delivery" and "reception". A) With the recent development of mice with genetically disrupted beta2-microglobulin beta2m-/-mice) and with the deficiency of MHC class I expression the data were accumulated which indicated the low functional significance of the CD8+ CTL in anti-virus and transplantation immunity. We found that in contrast to published reports, the intraperitoneal immunization of beta2-m-/-mice with alive tumor cells results in the accumulation of highly lytic and MHC class I specific CD8+CTL among peritoneal exudate lymphocytes (PEL) and in peripheral lymph organs. These CD8+CTL are similar to PEL CTL of normal mice in being responsible for tumor rejection except for the delay of tumor rejection in primary immune response and dramatic reduction of the Vbeta5 and Vbeta6 TCR phenotype usage. It is concluded that CD8+ CTL are major contributors in the anti-tumor immunity and that peritoneaum provides a very favorable environment for their development. These results emphasize the advantages of using CD8+ CTL in intraperitoneal adoptive immunotherapy. B) Poly ADP-rybose polymerse (PDDPRT) partially contributes into the CTL induced target cell death. The understanding of the mechanism of the TC death is important and we demonstrated that this enzyme is a part of a "suicidal" pathway, where CTL-induced DNA breaks, activate PADPRT which in turn depletes cellular NAD, ATP causing cell death. These results point to the PADPRT as possible target for immunomodulation, since the enhancement of PADPRT activity may result in more efficient lysis of tumor- or virus-infected cells by CTL.